Apigenin augments the growth inhibitory effects of doxorubicin in breast cancer cells derived from African American patients

B81

African American women are more prone to develop breast cancer at a younger age and present with a more aggressive, hormone-independent form of the disease than those belonging to other ethnic groups. Doxorubicin is commonly used in chemotherapeutic regimens to treat breast cancer irrespective of hormone receptor or p53 status. While patients with estrogen receptor (ER)-negative and progesterone receptor (PR)-negative breast cancer can derive benefit from using this agent, the onset of adverse effects can significantly diminish their quality of life. Some patients use herbal supplements containing flavonoids, while being treated with Doxorubicin, believing these products will potentiate its effectiveness. The purpose of our study was to determine whether the flavonoid Apigenin could suppress the growth of breast cancer cell lines derived from African American breast cancer patients with varying hormone receptor and p53 status and augment the anticancer effects of Doxorubicin in these cells. The cell lines included in this study were: ER-positive, PR-negative HCC70 cells containing wild-type p53; ER-negative, PR-negative MDA-MB-468 cells containing mutant p53; and the ER-negative, PR-negative HCC1806 and MDA-MB-157 cell lines that are p53 deficient. The ability of Apigenin alone, and in combination with Doxorubicin, to suppress the growth of the breast cancer cell lines was assessed. Both Apigenin and Doxorubicin inhibited the growth of all the breast cancer cell lines in the micromolar range as determined by the Alamar Blue™ reduction assay. Apigenin potentiated the growth inhibitory and apoptotic effects of Doxorubicin when co-treated with this agent as determined using phase-contrast microscopy and the Annexin V-PI assay. These results suggest that Apigenin may enhance the responsiveness of breast cancer patients to the anticancer effects of Doxorubicin including those with the more aggressive, hormone-independent form of the disease. Further studies are underway to correlate these observed changes with changes in expression of markers of apoptosis and proliferation such as BAX, bcl-2, ERK, PARP and survivin.